Clinical characteristics of the HAPE-p, HAPE-f and HLs.

<p>Data are presented as mean ± standard deviation and are compared by Student's <i>t</i>-test. n, number of subjects; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; RR, respiratory rate; PR, pulse rate; SaO₂, arterial oxygen saturation; PASP, pulmonary artery systolic pressure.</p

Interactions among Vascular-Tone Modulators Contribute to High Altitude Pulmonary Edema and Augmented Vasoreactivity in Highlanders

<div><h3>Background</h3><p>The interactions among various biomarkers remained unexplored under the stressful environment of high-altitude. Present study evaluated interactions among biomarkers to study susceptibility for high altitude pulmonary edema (HAPE) in HAPE-patients (HAPE-p) and adaptation in highland natives (HLs); both in comparison to HAPE-free sojourners (HAPE-f).</p> <h3>Methodology/Principal Findings</h3><p>All the subjects were recruited at 3500 m. We measured clinical parameters, biochemical levels in plasma and gene expression using RNA from blood; analyzed various correlations between and among the clinical parameters, especially arterial oxygen saturation (SaO₂) and mean arterial pressure (MAP) and biochemical parameters like, asymmetric dimethylarginine (ADMA), serotonin (5-HT), 8-iso-prostaglandin F2α (8-isoPGF2α), endothelin-1 (ET-1), plasma renin activity (PRA), plasma aldosterone concentration (PAC), superoxide dismutase (SOD) and nitric oxide (NO) in HAPE-p, HAPE-f and HLs. ADMA, 5-HT, 8-isoPGF2α, ET-1 levels, and PAC were significantly higher (p<0.0001, each), whereas SOD activity and NO level were significantly lower in HAPE-p than HAPE-f (p≤0.001). Furthermore, ADMA, 5-HT, 8-isoPGF2α, NO levels and PAC were significantly higher (p<0.0001), whereas ET-1 level significantly (p<0.0001) and SOD activity non-significantly (p>0.05) lower in HLs than HAPE-f. The expression of respective genes differed in the three groups. In the correlations, SaO₂ inversely correlated with ADMA, 5-HT and 8-isoPGF2α and positively with SOD in HAPE-p (p≤0.009). MAP correlated positively with 5-HT and 8-isoPGF2α in HAPE-p and HLs (p≤0.004). A strong positive correlation was observed between ADMA and 5-HT, 5-HT and 8-isoPGF2α (p≤0.001), whereas inverse correlation of SOD with ET-1 in HAPE-p and HLs (p≤0.004), with 5-HT and 8-isoPGF2α in HAPE-p (p = 0.01) and with 5-HT in HLs (p = 0.05).</p> <h3>Conclusions/Significance</h3><p>The interactions among these markers confer enhanced vascular activity in HLs and HAPE in sojourners.</p> </div

Clinical correlations in the three groups i.e. HAPE-p, HAPE-f and HLs.

<p>An inverse correlation was obtained between the clinical parameters viz MAP and SaO₂ in the three groups; MAP, mmHg; SaO₂, %.</p

Schematic presentation of the studied biomarkers in a physiological function under hypobaric hypoxia.

<p>Interactions of several of these biomarkers that translate into the incidence of HAPE are also interpretable through the renin–angiotensin–aldosterone system, Kinin–kallikrein system, and the pathways of ET-1, 5-HT, NO signaling and oxidative-stress. ADMA, asymmetric dimethylarginine; ATII, angiotensin II; AT-1R, angiotensin-II type I receptor; AT-2R, angiotensin-II type II receptor; AngI, angiotensin I; AngII, angiotensin II; ACE, angiotensin-I converting enzyme; AGT, angiotensinogen; 8-isoPGF2α, 8-iso-prostaglandinF2α; ROS, reactive oxygen species; SOD, superoxide dismutase; O2˙-, superoxide anion; ONOO⁻, peroxynitrite; 5-HT, serotonin; ET-1, endothelin-1; ET-_A and ET-_B, endothelin receptors A and B; NO, nitric oxide; NOS3, endothelial nitric oxide synthase; VSMC, vascular smooth muscle cell; H₂O₂, hydrogen peroxide; H₂O, water; EFA, essential fatty acids.</p

Baseline characteristics of the HAPE-p, HAPE-f and HLs.

<p>Data are presented as mean ± standard deviation and are compared by Student's <i>t</i>-test. n, number of subjects; BMI, body mass index.</p